Abstract

The F-box is a protein motif of approximately 50 amino acids that functions as a site
of protein-protein interaction. F-box proteins were first characterized as components
of SCF ubiquitin-ligase complexes (named after their main components, Skp I, Cullin,
and an F-box protein), in which they bind substrates for ubiquitin-mediated proteolysis.
The F-box motif links the F-box protein to other components of the SCF complex by
binding the core SCF component Skp I. F-box proteins have more recently been discovered
to function in non-SCF protein complexes in a variety of cellular functions. There
are 11 F-box proteins in budding yeast, 326 predicted in Caenorhabditis elegans, 22 in Drosophila, and at least 38 in humans. F-box proteins often include additional carboxy-terminal
motifs capable of protein-protein interaction; the most common secondary motifs in
yeast and human F-box proteins are WD repeats and leucine-rich repeats, both of which
have been found to bind phosphorylated substrates to the SCF complex. The majority
of F-box proteins have other associated motifs, and the functions of most of these
proteins have not yet been defined.